Muscle atrophy (sarcopenia) in the elderly is associated with a reduced rate of muscle protein synthesis (MPS), and weight lifting exercise increases the rate of MPS in 64-75 yr old men and women. The purpose of this study was to determine if weight lifting exercise increases the rate of muscle protein synthesis in physically frail old women. Before and after 3 mo. of weight lifting exercise, MPS was determined during a constant intravenous infusion of 1-[13C]leucine. The in vivo incorporation rate of 13C-leucine into vastus lateralis muscle protein was (a) elevated at baseline (0.048(0.004 vs 0.030(0.003%h), perhaps as a result of the physical therapy program; and (b) increased to 0.104(0.028%h (P0.05) after the 3 mo. weight training program, while it was not changed in a control subject. This suggests that weight lifting exercise increases muscle protein synthesis rate and REE in physically frail 78-92 yr old women with muscle wasting.